1,027 research outputs found

    Size-structured risk assessments govern Daphnia migration

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    One of the more fascinating phenomena in nature is animal mass migrations and in oceans and freshwaters, diel variations in depth distribution of zooplankton are a phenomenon that has intrigued scientists for more than a century. In our study, we show that zooplankton are able to assess the threat level of ultraviolet radiation and adjust their depth distribution to this level at a very fine tuned scale. Moreover, predation risk induces a size-structured depth separation, such that small individuals, which we show are less vulnerable to predation than larger, make a risk assessment and continue feeding in surface waters during day, offering a competitive release from down-migrating larger animals. Hence, we mechanistically show that such simple organisms as invertebrate zooplankton are able to make individual, size-specific decisions regarding how to compromise between threats from both predators and UV radiation, and adjust their diel migratory patterns accordingly

    Efficacy of rHuIFN-alpha2b and rFeIFN-omega on Feline Herpesvirus-1 Replication in vitro

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    Feline herpesvirus-1 (FHV-1)-infection, also known as feline viral rhinotracheitis (FVR) is distributed world wide in the cat population, with a high incidence in colony cats (>70%). FHV-1 typically infects and replicates in epithelial tissue of the upper respiratory tract and conjunctiva causing cytopathic lesions. The virus is recognized as one of the most important pathogens of feline upper respiratory tract infections, conjunctivitis and keratitis in cats. Following primary infection over 80% of cats are unable to eliminate the virus and develop a carrier state, with intermittent episodes of virus shedding. During latency, the virus persists most often in the trigeminal ganglion and the disease can be reactivated following stress and corticosteroid therapy. Successful treatment, particularly of ocular manifestations associated with recrudescent infection such as dendritic ulcers remains difficult. Available antiviral drugs are virostatic and in particular, the systemic application is associated with severe toxic side effects. Human natural and recombinant interferons and feline interferons have been described in their use against a selection of feline and canine viruses (JAMESON and ESSEX, 1983; FULTON and BURGE, 1985; WEISS and TOIVIO-KINNUCAN, 1988; WEISS, 1989; WEISS and OOSTROM-RAM, 1990; TRUYEN et al., 2001). To date, only two in vitro studies indicate a potent antiviral activity of the recombinant FeIFN-ω against FHV-1 (MOCHIZUKI et al., 1994, TRUYEN et al., 2001). The purpose of this study was to evaluate the antiviral efficacy of the recently available rFeIFN-ω (Virbagen®-ω) and the human rHuIFN-α2b (Intron®-A) on the replication of FHV-1 in vitro. A wider range of concentrations (100 U/ml – 500,000 U/ml) was studied than used in the previous studies (WEISS , 1989; MOCHIZUKI et al., 1994, TRUYEN et al., 2001) in order to repeat previously tested concentration and further, to determine whether the drugs have a dose-dependant response of antiviral activity and which concentration would be the most effective treatment. The species-specificity of type I interferons is well known and therefore, it was suggested that rFeIFN-ω would result in a more profound effect compared to the rHuIFN-α2b due to its homologous nature. In addition to cell and virus culture techniques, a methodology for the plaque reduction assay was established. Furthermore, for the first time antiviral efficacy for interferon was additionally measured by plaque size reductions and is reported in this study. An in vitro MTT-Assay was integrated in the experiment to exclude possible cytotoxic effects that could, in principle, contribute to the antiviral effects observed with either of the interferon treatments. For the plaque reduction assay, confluent monolayers of Crandell feline kidney (CRFK)-cells were grown in 24-well cell culture plates. Cells were treated with either rFeIFN-ω (Virbagen® Omega) or rHuIFN-α2b (Intron®-A) across a set of serial dilutions (100 U/ml - 500,000 U/ml). Cells were treated six hours before addition of FHV-1, concurrent with addition of FHV-1 and each drug concentration was added to the overlay medium (2X DMEM 1:1 with 1.6% Agarose). The treatments were performed in duplicates including virus controls, which received PBS instead of either one of the interferons and assays were performed on six occasions. Following incubation of 72 hrs, the cells were fixed with formalin, overlay plugs were discarded and the remaining cell layers were stained with crystal violet. Plaque numbers were counted under an inverted microscope and Plaque diameters were measured using a reticule. For the MTT-assay, 96-well culture plates were seeded with CRFK-cells. In each of the test wells (n=16) growth medium was supplemented with either rHuIFN-α2b or with rFeIFN-ω. Control wells (n=72) received growth medium with PBS instead of either one of the Interferons. Cell-death controls were treated with ethanol to obtain 100% cell death. After incubation, the medium was aspirated and replaced with medium containing the MTT-solution. Following another incubation period, the medium of each well was removed and replaced with a solubilization solution (0.1N HCL/Isopropanol). The plates were incubated for an additional five minutes to dissolve the crystals and the plates were read using a plate reader. The average optical densities were calculated for each dilution and compared with that of the positive control wells. A one-way ANOVA and Dunnett’s test were used for the statistical analysis of all experiments. A significant reduction of plaque numbers was observed for rFeIFN-ω at 100,000 U/ml with a plaque reduction of 54.7 % and at 500,000 U/ml with a plaque reduction of 59.8 %. Plaque sizes were significantly reduced by 47.5 % at 100,000 U/ml and by 81 % at 250,000 U/ml and 70.5% at 500,000 U/ml. Recombinant HuIFN-α2b treatment did not succeed to produce any significant plaque number reduction. However, significant plaque size reductions were observed following treatment with 100,000 U/ml, 250,000 U/ml and 500,000 U/ml with reductions of 56 %, 75.7% and 69% respectively. None of the high-dose treatments of either rHuIFN-α2b or rFeIFN-ω caused significant cellular toxicity in the MTT-Assay. Therefore, the antiviral activity demonstrated by both interferons is not attributable to an in vitro effect on the cellular viability of CRFK-cells. In agreement with previous authors, this study was able to demonstrated that rFeIFN-ω and rHuIFN-α2b have inhibitory effects on the replication of FHV-1. For rFeIFN-ω the antiviral effect is dose-dependent and could be reliably detected at high concentrations (> 50,000 U/ml) using both the plaque number and plaque size measurements. Treatment with high concentrations of rHuIFN-α2b also resulted in an antiviral effect, which was only detected at using the plaque size measure; there was no statistical evidence for a reduction in the plaque number measurement. The significantly smaller plaque sizes in drug–treated cell cultures indicate that high-dose treatment with rFeIFN-ω or rHuIFN-α2b may have potential efficacy on reducing the dimensions of FHV-1 induced cytopathic lesions. Treatment with rFeIFN-ω has shown more profound effects in antiviral activity compared to rHuIFN-α2b and, in contrast to rHuIFN-α2b, it also offers the advantage of a homologous compound. This is consistent with recently published results obtained on in vivo activity, which have demonstrated that high-dose treatment of rFeIFN-ω shows good antiviral efficacy and clinical improvement (VERNEUIL, 2004; BRAECKLEIN et al., 2003). Therefore, there are indications that rFeIFN-ω may provide effective prophylactic and therapeutic treatment for FHV-1 infected cats.Das feline Herpesvirus-1 (FHV-1) ist ein weltweit bei Katzen vorkommendes DNA-Alphaherpesvirus, das neben den Oberflaechenepithelien des Respirationstrakts auch die Konjunktiven infiziert. Der Erreger stellt eine der wichtigsten Ursachen des Katzenschnupfens dar und wird als haeufigste Aetiologie bei der Konjunktivitis und auch der Keratits der Katze nachgewiesen. Vor allem bei Tieren, die in Gruppen gehaltenen werden, ist eine hohe Inzidenz (> 70 %) feststellbar. Im Anschluss an eine Primaerinfektion entwickeln fast alle Katzen (> 80 %) einen Traegerstatus. In der Latenzphase persistiert das Virus hauptsaechlich im Trigeminalganglion, aus dem es spontan oder durch eine Reihe anderer Ursachen (u.a. Stress, Cortisontherapie) zu einer Reaktivierung der Erkrankung und Virusausscheidung kommen kann. Eine Therapie der FHV-1 Infektion mit Virostatika (z.B. Aciclovir) ist sowohl systemisch als auch lokal moeglich, aber umstritten, da sie in einigen Faellen nur geringe Wirkung zeigt, und die systemische Anwendung mit erheblichen toxischen Nebenwirkungen verbunden ist. Die erfolgreiche Behandlung, vor allem der bei persistierenden Infektionen wiederkehrenden okulaeren Manifestationen, stellt eine therapeutische Herausforderung dar. In der Literatur wird die Anwendung humaner und feliner Interferone und ihre antivirale Wirkung gegen ausgewaehlte feline und canine Viren beschrieben (JAMESON & ESSEX, 1983; FULTON & BURGE, 1985; WEISS & TOIVIO-KINNUCAN, 1988; WEISS, 1989; WEISS & OOSTROM-RAM, 1990; TRUYEN ET AL., 2001). Bisher existieren aber nur zwei in vitro Studien, die auf eine vielversprechende Wirkung des rFeIFN-ω in der Behandlung der FHV-1 Infektion hinweisen (MOCHIZUKI ET AL., 1994; TRUYEN ET AL., 2001). Es war Ziel dieser Studie, den antiviralen Effekt des humanen rHuIFN-α2b (Intron®-A) sowie des felinen rFeIFN-ω (Virbagen®-ω) auf die Replikation von FHV-1 in vitro zu untersuchen und miteinander zu vergleichen. Dabei sollte im Gegensatz zu bisherigen Untersuchungen (WEISS, 1989; MOCHIZUKI ET AL., 1994, TRUYEN ET AL., 2001) die Wirkung eines breiteren Spektrums (100 U/ml – 500,000 U/ml) von Interferon-Konzentrationen untersucht werden. Dieses Spektrum wurde gewaehlt, um beschriebene Konzentrationen zu wiederholen und um zu untersuchen, ob eine dosisabhaengige Wirkung sowie eine eventuell optimale Dosis der Interferone vorlaegen. Aufgrund der engen Spezies-Spezifitaet wurde bei der Behandlung mit dem homologen rFeIFN-ω im Vergleich zu dem heterologen rHuIFN-α2b ein deutlicherer Effekt erwartet. Der Plaquereduktionstest sowie alle Zell- und Viruskultur-Techniken mussten dazu vor Beginn der Experimente etabliert werden. Ausserdem konnte erstmals gezeigt werden, dass die antivirale Wirksamkeit von Interferon auch anhand der Plaquegroesse quantifiziert werden kann. Um einen Zusammenhang zwischen einem antiviralen Effekt und einer zelltoxischen Wirkung beider Interferone auszuschliessen, wurde die Zellstoffwechselaktivitaet behandelter im Vergleich zu unbehandelter Zellkulturen in MTT-Assays untersucht. Im Plaquereduktionstest wurde die Wirkung von jeweils 12 abgestuften Konzentrationen (100 U/ml bis 500.000 U/ml) pro Interferon (rFeIFN-ω, rHuIFN-α2b) in Duplikaten untersucht und sechsmal wiederholt. Dazu wurden CRFK-Zellen in 24-Zellkultur-Lochplatten ausgesaet und ueber Nacht inkubiert. Die Zugabe der jeweiligen Interferonloesungen erfolgte sechs Stunden vor Virusinkubation und wurde ueber den weiteren Verlauf des Versuchs aufrechterhalten. Als Kontrolle dienten CRFK-Zellen, die jeweils an Stelle von Interferon phosphat-gepufferte Kochsalzloesung (PBS) erhielten, abgesehen davon aber den gleichen experimentellen Bedingungen ausgesetzt waren wie die Versuchsgruppen. Im Anschluss an die 72 stuendige Inkubation wurden die Zellen fixiert, das Overlay-Medium wurde entfernt und die Zellrasen mit Kristallviolett gefaerbt. Die Anzahl der Plaques (pro Vertiefung und Interferonkonzentration) konnte unter dem invertierten Lichtmikroskop gezaehlt und anschliessend ausgewertet werden. Die Erfassung einzelner Plaquesdurchmesser erfolgte mikroskopisch mit einem Meβokular. Das MTT-Assay wurde in 96-Mikrotiterplatten mit CRFK–Zellen durchgefuehrt. Die Wirkung der Interferone wurde fuer jede Konzentration in acht Parallelansaetzen (n=16) ermittelt und zweimal durchgefuehrt. Als Referenz dienten eine Lebend-kontrollgruppe, in der die Interferonbehandlung durch PBS ersetzt wurde und eine Totkontrollgruppe, in der die Zellen mit Ethanol abgetoetet worden waren. Die Mikrotiterplatten wurden inkubiert und anschliessend wurde das Medium durch MTT-haltiges Medium ersetzt. Nach weiterer Inkubation wurde das Medium durch einer HCL/Isopronalol-Loesung ersetzt, um die Kristalle aufzuloesen. Die optischen Dichten in den Vertiefungen wurden spektrophotometrisch gemessen. Anschliessend wurden die mittleren optischen Dichten errechnet und mit den Kontrollwerten verglichen. Zur statistischen Auswertung der Experimente wurde eine ANOVA und der Dunnett-Test herangezogen. Eine signifikante Plaquezahlreduktion konnte nur in den mit rFeIFN-ω behandelten Zellkulturen festgestellt werden. In den Konzentrationen 100.000 U/ml und 500.000 U/ml ergab die Anzahl der Plaques eine Reduktion um 54,7 % (p<0,05) bzw. um 59,8 % (p<0,05) gegenueber den unbehandelten Kontrollen. Ausserdem konnte eine statistisch signifikante Reduktion der Plaquegroeβe bei 100.000 U/ml von 47,5 %, bei 250.000 U/ml von 81 % und bei 500.000 U/ml von 70,5 % gegenueber den unbehandelten Kontrollen festgestellt werden. rHuIFN-α2b induzierte in keiner der untersuchten Konzentrationen eine signifikante Plaquezahlreduktion. Dagegen konnte jedoch eine signifikante Reduktion der Plaquegroeβe bei den Behandlungen mit 100.000 U/ml, 250.000 U/ml, und 500.000 U/ml um 56,4 %, bzw. um 75,7 %, und um 69,8 % nachgewiesen werden. Die optischen Dichten fuer rFeIFN-ω und rHuIFN-α2b waren fuer alle gemessenen Konzentrationen signifikant (p<0,05) uebereinstimmend mit den optischen Dichten der Lebendkontrollgruppen und signifikant hoeher (p<0,05) verglichen mit den Werten der Totkontrollgruppe. Damit ist gezeigt worden, dass sowohl rFeIFN-ω als auch rFeIFN-α2b keine signifikante zelltoxische Auswirkung auf den Zellstoffwechsel hatte. Mit dieser Arbeit ist es im wesentlichen gelungen, die antivirale Wirkung von rFeIFN sowie von rHuIFN-α2b auf die Replikation von FHV-1 zu bestaetigen. Eine Dosis-Wirkungsbeziehung des rFeIFN-ω, sowie statistisch signifikanter Reduktion der Plaquezahl und Plaquegroeβe konnte bei Behandlung mit hohen Konzentrationen (> 50.000 U/ml) von Interferon beobachtet werden. Mit der rHuIFN-α2b-Behandlung konnte keine statistisch signifikante Plaquezahlreduktion, aber eine signifikante Reduktion der Plaquegroeβe nach Applikation hoher Konzentrationen (> 50.000 U/ml) festgestellt werden. Erst kuerzlich wurde in zwei in vivo Studien von einer guten antiviralen Wirkung hoher rFeIFN-ω Konzentrationen berichtet, welche die Ergebnisse der vorliegenden Studie bestaetigen (BRAECKLEIN ET AL., 2003; VERNEUIL, 2004). Somit liegt die Vermutung nahe, dass besonders mit dem rFeIFN-ω ein Praeparat zur Verfuegung steht, das bei prophylaktischer und kontinuierlicher Applikation im Verlauf einer Infektion in der Lage ist, die Ausbreitung von Nachkommenviren und damit die Ausdehnung der zytotoxischen Laesionen in infiziertem Gewebe in vitro einzuschraenken

    Concepts for the Representation, Storage, and Retrieval of Spatio-Temporal Objects in 3D/4D Geo-Informations-Systems

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    The quickly increasing number of spatio-temporal applications in fields like environmental management or geology is a new challenge to the development of database systems. This thesis addresses three areas of the problem of integrating spatio-temporal objects into databases. First, a new representational model for continuously changing, spatial 3D objects is introduced and transferred into a small system of classes within an object-oriented database framework. The model extends simplicial cell complexes to the spatio-temporal setting. The problem of closure under certain operations is investigated. Second, internal data structures are introduced that represent instances of the (user-level) spatio-temporal classes. A new technique provides a compromise between compact storage and efficient retrieval of spatio-temporal objects. These structures correspond to temporal graphs and support updates as well as the maintainance of connected components over time. Third, it is shown how to realise further operations on the new type of objects. Among these operations are range queries, intersection tests, and the Euclidean distance function

    Fish are flexible learners who can discriminate human faces

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    In his book “What a fish knows” Jonathan Balcombe (2016a, b) has created a comprehensive profile of a group of animals still often thought to have a 3-second memory, no ability to feel pain, and a generally limited ability to learn. Chapter by chapter, Balcombe dismantles these and other such assumptions and makes a convincing case that fish have many abilities that are not that different from our own. Here, I focus on one example which supports the notion that fish are flexible learners and able to perform tasks which are generally thought to require the advanced processing power of the primate cortex. Archerfish and damselfish are able to discriminate human faces, even when the faces are partly obscured by artificial noise, rotated or presented as standardised greyscale images. This demonstrates that the machinery for the visual analysis and processing of objects is present in fish and leads to the question of why this machinery was transferred to the cortex in primates

    Fish are flexible learners who can discriminate human faces

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    In his book “What a fish knows” Jonathan Balcombe (2016a, b) has created a comprehensive profile of a group of animals still often thought to have a 3-second memory, no ability to feel pain, and a generally limited ability to learn. Chapter by chapter, Balcombe dismantles these and other such assumptions and makes a convincing case that fish have many abilities that are not that different from our own. Here, I focus on one example which supports the notion that fish are flexible learners and able to perform tasks which are generally thought to require the advanced processing power of the primate cortex. Archerfish and damselfish are able to discriminate human faces, even when the faces are partly obscured by artificial noise, rotated or presented as standardised greyscale images. This demonstrates that the machinery for the visual analysis and processing of objects is present in fish and leads to the question of why this machinery was transferred to the cortex in primates

    FTEs: Theory, Simulation, and Observations

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    Flux transfer events (FTEs) are ropes of interconnected magnetosheath and magnetospheric magnetic field lines generated by bursty reconnection at the dayside magnetopause. Theory predicts that the combined pressure gradient and magnetic curvature forces should determine the speed at which the events move and the locations where they can be observed. We present results indicating that events form on the dayside magnetopause for both northward and southward IMF orientations, but that the events for northward IMF orientations exhibit far weaker signatures until they reach the magnetospheric flanks and argue that this is consistent with observations indicating that events on the dayside tend to occur for southward IMF orientations, but those on the flank do not. We show that the component and antiparallel reconnection models predict events in strikingly different quadrants outside the flanks of the magnetotail.Observations of events in all four quadrants indicate that both models are required. The motion of events inferred from multispacecraft timing during periods of northward IMF orientation is generally consistent with the component reconnection model
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